title: Aurintricarboxylic acid inhibits complement activation, membrane attack complex, and choroidal neovascularization in a model of macular degeneration.
abstract: OBJECTIVE
  Immunocytochemical and genetic data implicate a significant role for the activation of complement in the pathology of AMD. Individuals homozygous for a Y402H polymorphism in Factor H have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and RPE relative to individuals homozygous for the wild-type allele. An R95X polymorphism in C9, a protein necessary for the final assembly of MAC, is partially protective against the formation of choroidal neovascularization (CNV) in AMD patients. Aurintricarboxylic Acid (ATA) is a small molecule inhibitor of MAC. Our hypothesis was that attenuation of the formation of MAC on ocular tissues by ATA may protect mice against laser-induced CNV.
  
  
  METHODS
  The ability of ATA to inhibit human complement-mediated cell lysis, inhibit formation of human MAC, and inhibit formation of tubes by endothelial cells was examined in vitro. Subsequently, the Bruch's membrane of adult mice was damaged using an argon laser, followed by intravitreal injection of ATA. One week later, choroidal flat mounts from these mice were stained for the presence of MAC, endothelial cells, and macrophages.
  
  
  RESULTS
  ATA protects cells from human complement-mediated lysis, attenuates assembly of the MAC, and inhibits tube formation by endothelial cells in vitro. ATA also attenuates CNV, MAC deposition, and macrophage infiltration in a murine model of exudative AMD.
  
  
  CONCLUSIONS
  ATA warrants further study as a potential drug for the treatment of exudative and nonexudative AMD.
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Erion
authors.initials: E
authors.lastname: Lipo
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Cashman
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kumar-Singh
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000517:prevention & control*; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015938:Complement Membrane Attack Complex; D001312:Aurintricarboxylic Acid
keywords: aurintricarboxylic acid; choroidal neovascularization; complement; macular degeneration; membrane attack complex